Silver nanoparticles: correlating nanoparticle size and cellular uptake with genotoxicity

Abstract

The focus of this research was to develop a better understanding of the pertinent physico-chemical properties of silver nanoparticles (AgNPs) that affect genotoxicity, specifically how cellular uptake influences a genotoxic cell response. The genotoxicity of AgNPs was assessed for three potential mechanisms: mutagenicity, clastogenicity and DNA strand-break-based DNA damage. Mutagenicity (reverse mutation assay) was assessed in five bacterial strains of Salmonella typhimurium and Echerichia coli, including TA102 that is sensitive to oxidative DNA damage. AgNPs of all sizes tested (10, 20, 50 and 100nm), along with silver nitrate (AgNO3), were negative for mutagenicity in bacteria. No AgNPs could be identified within the bacteria cells using transmission electron microscopy (TEM), indicating these bacteria lack the ability to actively uptake AgNPs 10nm or larger. Clastogenicity (flow cytometry-based micronucleus assay) and intermediate DNA damage (DNA strand breaks as measured in the Comet assay) were assessed in two mammalian white blood cell lines: Jurkat Clone E6-1 and THP-1. It was observed that micronucleus and Comet assay end points were inversely correlated with AgNP size, with smaller NPs inducing a more genotoxic response. TEM results indicated that AgNPs were confined within intracellular vesicles of mammalian cells and did not penetrate the nucleus. The genotoxicity test results and the effect of AgNO3 controls suggest that silver ions may be the primary, and perhaps only, cause of genotoxicity. Furthermore, since AgNO3 was not mutagenic in the gram-negative bacterial Ames strains tested, the lack of bacterial uptake of the AgNPs may not be the major reason for the lack of genotoxicity observed.

Immunotoxic effects of gold and silver nanoparticles: Inhibition of mitogen-induced proliferative responses and viability of human and murine lymphocytesin vitro

“…Interestingly, GNP selectively inhibited the proliferation of myeloma cells, but had no effect on the proliferation of human peripheral blood lymphocytes (PBL) . Similarly, exposure of experimental animals to SNP has been shown to cause anemia, cardiac enlargement, growth retardation and degenerative changes in the liver (Butler et al 2015). With regard to the immune system, the viability of human PBL was decreased in time-and dose-dependent manners upon exposure to SNP in vitro (Ghosh et al 2012;Vergallo et al 2014;Zhornik et al 2014).…”

Nanosilver: new ageless and versatile biomedical therapeutic scaffold

“…Currently, nanoscale materials have achieved considerable attention as novel antimicrobial agents due to their high surface area-to-volume ratio and distinct physical and chemical properties. [5][6][7] The extremely strong broad-spectrum antimicrobial property of AgNPs is the key direction for the improvement of AgNPs-based biomedical products, including bandages, catheters, antiseptic sprayers, textiles, and food storage containers. and pyrolysis; 21 of these, chemical reduction has been the most common route to synthesize nanosilver.…”

Particle coatings but not silver ions mediate genotoxicity of ingested silver nanoparticles in a mouse model

“…long-term health effects, especially, cancer. Studies that utilized the Ames test measuring point mutations in bacterial stains of S. typhimurium and/or E. coli reported that AgNPs tested negative for mutagenicity in bacteria (Butler et al, 2015; Guo et al, 2016). The lack of mutagenicity was explained by the inability of bacteria to take up AgNPs (Butler et al, 2015; Guo et al, 2016).…”

“…Studies that utilized the Ames test measuring point mutations in bacterial stains of S. typhimurium and/or E. coli reported that AgNPs tested negative for mutagenicity in bacteria (Butler et al, 2015; Guo et al, 2016). The lack of mutagenicity was explained by the inability of bacteria to take up AgNPs (Butler et al, 2015; Guo et al, 2016). However, AgNPs induced mutagenic and clastogenic effects in mammalian cells as shown by mouse lymphoma and micronucleus assays, respectively (Butler et al, 2015; Guo et al, 2016; Vecchio et al, 2014).…”